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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Hunna J Watson, Zeynep Yilmaz, Laura M Thornton, Christopher Hübel, Jonathan R I Coleman, Héléna A Gaspar, Julien Bryois, Anke Hinney, Virpi M Leppä, Manuel Mattheisen, Sarah E Medland, Stephan Ripke, Shuyang Yao, Paola Giusti-Rodríguez, Ken B Hanscombe, Kirstin L Purves, Roger A H Adan, Lars Alfredsson, Tetsuya Ando, Ole A Andreassen, Jessica H Baker, Wade H Berrettini, Ilka Boehm, Claudette Boni, Vesna Boraska Perica, Katharina Buehren, Roland Burghardt, Matteo Cassina, Sven Cichon, Maurizio Clementi, Roger D Cone, Philippe Courtet, Scott Crow, James J Crowley, Unna N Danner, Oliver S P Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece E DeSocio, Danielle M Dick, Dimitris Dikeos, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo, Laramie E Duncan, Karin Egberts, Stefan Ehrlich, Geòrgia Escaramís, Tõnu Esko, Xavier Estivill, Anne Farmer, Angela Favaro, Fernando Fernández-Aranda, Manfred M Fichter, Krista Fischer, Manuel Föcker, Lenka Foretova, Andreas J Forstner, Monica Forzan, Christopher S Franklin, Steven Gallinger, Ina Giegling, Johanna Giuranna, Fragiskos Gonidakis, Philip Gorwood, Monica Gratacos Mayora, Sébastien Guillaume, Yiran Guo, Hakon Hakonarson, Konstantinos Hatzikotoulas, Joanna Hauser, Johannes Hebebrand, Sietske G Helder, Stefan Herms, Beate Herpertz-Dahlmann, Wolfgang Herzog, Laura M Huckins, James I Hudson, Hartmut Imgart, Hidetoshi Inoko, Vladimir Janout, Susana Jiménez-Murcia, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Jaakko Kaprio, Leila Karhunen, Andreas Karwautz, Martien J H Kas, James L Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Youl-Ri Kim, Lars Klareskog, Kelly L Klump, Gun Peggy S Knudsen, Maria C La Via, Stephanie Le Hellard, Robert D Levitan, Dong Li, Lisa Lilenfeld, Bochao Danae Lin, Jolanta Lissowska, Jurjen Luykx, Pierre J Magistretti, Mario Maj, Katrin Mannik, Sara Marsal, Christian R Marshall, Morten Mattingsdal, Sara McDevitt, Peter McGuffin, Andres Metspalu, Ingrid Meulenbelt, Nadia Micali, Karen Mitchell, Alessio Maria Monteleone, Palmiero Monteleone, Melissa A Munn-Chernoff, Benedetta Nacmias, Marie Navratilova, Ioanna Ntalla, Julie K O'Toole, Roel A Ophoff, Leonid Padyukov, Aarno Palotie, Jacques Pantel, Hana Papezova, Dalila Pinto, Raquel Rabionet, Anu Raevuori, Nicolas Ramoz, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Franziska Ritschel, Marion Roberts, Alessandro Rotondo, Dan Rujescu, Filip Rybakowski, Paolo Santonastaso, André Scherag, Stephen W Scherer, Ulrike Schmidt, Nicholas J Schork, Alexandra Schosser, Jochen Seitz, Lenka Slachtova, P Eline Slagboom, Margarita C T Slof-Op 't Landt, Agnieszka Slopien, Sandro Sorbi, Beata Świątkowska, Jin P Szatkiewicz, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Janet Treasure, Artemis Tsitsika, Marta Tyszkiewicz-Nwafor, Konstantinos Tziouvas, Annemarie A van Elburg, Eric F van Furth, Gudrun Wagner, Esther Walton, Elisabeth Widen, Eleftheria Zeggini, Stephanie Zerwas, Stephan Zipfel, Andrew W Bergen, Joseph M Boden, Harry Brandt, Steven Crawford, Katherine A Halmi, L John Horwood, Craig Johnson, Allan S Kaplan, Walter H Kaye, James E Mitchell, Catherine M Olsen, John F Pearson, Nancy L Pedersen, Michael Strober, Thomas Werge, David C Whiteman, D Blake Woodside, Garret D Stuber, Scott Gordon, Jakob Grove, Anjali K Henders, Anders Juréus, Katherine M Kirk, Janne T Larsen, Richard Parker, Liselotte Petersen, Jennifer Jordan, Martin Kennedy, Grant W Montgomery, Tracey D Wade, Andreas Birgegård, Paul Lichtenstein, Claes Norring, Mikael Landén, Nicholas G Martin, Preben Bo Mortensen, Patrick F Sullivan, Gerome Breen, Cynthia M Bulik
Nature Genetics 2019, 51 (8): 1207-1214
31308545
Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1 , affecting 0.9-4% of women and 0.3% of men2-4 , with twin-based heritability estimates of 50-60%5 . Mortality rates are higher than those in other psychiatric disorders6 , and outcomes are unacceptably poor7 . Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

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